A Amino Acid Metabolism B Ammonia Metabolism and 13NH3 as a Perfusion Marker Amino acid and ammonia metabolism will be studied in isolated perfused rabbit interventricular septa. These studies will provide insight into the biology of these substances in the heart and serve as isolated muscle preparations in which isotopic exchange can be modeled in conjunction with applications in the intact dog and in man. Shine and coworkers have demonstrated a protective effect of the amino acids glutamate, asparate, arginine and ornithine upon mechanical performance after ischemia or anoxia in isolated perfused heart muscle. Two of these amino acids, arginine and ornithine, are metabolized to glutamate and may play an important role in urea metabolism or in anaerobic substrate phosphorlyation. Aspartate interacts with glutamate in the malateaspartate shuttle and in the tricarboxycyclic acid cycle. The proposed research seeks to define the potential usefulness of these amino acids as marker of ischemia or anoxia. The tissue content and kinetics of amino acid uptake in isolated perfused rabbit interventricular septa will be studied during ischemia, anoxia, reoxygenation, and reperfusion. The relationship between the amino acids and high energy phosphate production, anaerobic glycolyosis, ammino detoxication and mechanical recovery will be examined. The role of these amino acids in the exchange of calcium in ischemic or anoxic myocardium will be studied. The isolated septum has already been used to document the flow dependence of 13NH3 extraction in oxygenated tissue. Project B will address the metabolic rates of injected 13NH3 and examine the factors which control its uptake, metabolism and release from the myocardium. The effects of anoxia and ischemia on 13NH3 uptake and metabolism will be explored. Theoretical models for 13NH3 exchange can be tested in the isolated system.